醛固酮合成酶基因及环境因素对高血压交互作用

Effects genetic polymorphisms of CYP11B2 and enviromental factors on development of essential hypertension

目的探讨汉族人群醛固酮合成酶基因(CYP11B2)启动子区-344C/T和第三外显因子K173R多态性位点与原发性高血压(EHT)关系。方法按病例对照研究方法选择来自黑龙江省哈尔滨市的2组人群(210例EHT患者和391名对照及补充的182例EHT患者和189名对照),利用聚合酶链反应-限制性片段长度多态性及直接测序技术分别对其进行-344C/T与K173R基因型检测,问卷调查和实验室检查获取传统危险因素。结果总人群和男性中,-344C/T基因型分布在高血压组和对照组间差异均有统计学意义(P<0.05),而K173R基因型分布仅在女性高血压组和对照组间差异有统计学意义(χ2=11.16,P=0.003 8);总人群中,-344C/T CC+TC、K173RKK分布与体质指数、腰围、血脂异常、高血糖对EHT均存在正交互作用,饮酒、吸烟与-344C/T CC+TC分布同时出现对EHT发生有促进作用;按性别分组的亚群中,除男、女血脂异常、女性血糖升高与-344C/T CC+TC分布同时存在对EHT存在负交互作用外,其余均为正交互作用。结论 -344C/T、K173R基因多态性分布在汉族EHT与正常人群中存在差异;-344 C/T CC+TC、K173R KK与传统危险因素联合作用可促进EHT发生。

Objective To explore the relationship between genetic polymorphisms of-344C/T in the promoter region,K173R in the exon-3 of aldosterone synthase gene（CYP11B2） and essential hypertension（EHT）,and to identify whether classical risk factors interact with genetic polymorphisms in the development of the disease.Methods We used a nested case-control design to investigate the relationship between genetic polymorphisms of-344C/T,K173R and the risk of EHT.The genetic polymorphisms were detected with polymerase chain reaction-restriction fragment length polymorphism（PCR-RELP） in 210 EHT patients and 391 normal controls（182 complemental cases and 189 matched controls） from Harbin city.Information on several classical risk factors were collected.Results The differences in 344C/T genotype frequency distribution between EHT patients and normal controls were statistically significant in men and all subjects（P0.05）.The difference in K173R genotype frequency distribution between EHT patients and normal controls was statistically significant in women（P0.01）.Overall,there were several synergistic effects between the studied polymorphisms and classical risk factors,including overweight,abdomen obesity,hyperglycemia and dyslipidemia.The presence of-344C/T CC＋TC（and also K173R KK） increased the odds of developing EHT when combined with the classical risk factors（synergism index1）.Alcohol drinking and smoking also increased the risk of EHT in the presence of-344C/T CC＋TC.In the subgroup analyses,dyslipidemia interacted negatively with-344C/T CC＋TC for both men and women,and hyperglycemia interacted negatively with-344C/T CC＋TC in women.In addition,the risk factors interacted positively with-344C/T CC＋TC as well as K173R KK.Conclusion The differences in-344C/T and K173R genotype frequency distributions between EHT patients and normal controls are statistically significant in Han people.Moreover,the combined effects of-344C/T CC＋TC,K173R KK,and some classical risk factors significantly contribute to the development of the EHT.